It is becoming common for whole blood collected from a donor to be separated into blood component preparations such as an erythrocyte preparation, a thrombocyte preparation, and a blood plasma preparation and stored for transfusion. Since microaggregates and leukocytes included in these blood preparations cause various side effects during blood transfusion, the number of occasions for removing these undesirable components before blood transfusion has been increasing. The need for leukocyte removal has widely been recognized particularly in recent years. Legislation regarding removal of leukocytes from all kinds of blood preparations for blood transfusion before being used for transfusion has been introduced in an increasing number of countries.
The most common method of removing leukocytes from blood preparations is by processing blood preparations using a leukocyte removal filter. Conventionally, in many cases blood preparations processed using a leukocyte removal filter have been processed at the bedside when blood transfusion is performed. In recent years, however, to improve quality control of leukocyte-free preparations and efficiency of leukocyte removal operations, it is more common, particularly in developed countries, to process the blood preparations in blood centers before storing the blood preparations (pre-storage leukocyte removal).
A blood collection-separation set, typically consisting of two to four flexible bags, a tube connecting these bags, an anticoagulant, an erythrocyte preservation solution, a blood collection needle, and the like has been used for collecting blood from a donor, separating the blood into several blood components, and storing the blood components. A system in which a leukocyte removal filter is incorporated into such a blood collection-separation set has been widely used as an optimum system for the above-mentioned “pre-storage leukocyte removal”. Such a system is called a “closed system” or an “integrated system” or the like. Such systems are disclosed in Japanese Patent Laid-Open No. 1-320064, International Publication No. WO 92/020428 and the like.
Conventionally, a filter element made from nonwoven fabric or a porous body packed in a hard container of polycarbonate or the like has been widely used as a leukocyte removal filter. However, because the container used in such a filter has a low level of air permeability, there is the problem that it is difficult to apply steam sterilization, which is widely used as a sterilization process in blood collection-separation sets. In one type of closed system, leukocytes are first removed from the whole blood preparation after collecting the blood. Subsequently, after the leukocyte removal filter is separated, the leukocyte-free blood is centrifuged for separation into various components. In another type of closed system, the whole blood is first centrifuged to be divided into various blood components, and then the leukocytes are removed. In the latter system, the leukocyte removal filter is also centrifuged together with the blood collection-separation set. At such time, a hard container may damage bags and tubes, or the hard container itself may not withstand the stress and may break during centrifugation.
To solve these problems, flexible leukocyte removal filters have been developed in which the container is made of a material having excellent flexibility and steam permeability that is the same as or similar to the material used for the bags of the blood collection-separation set. These flexible leukocyte removal filters that use a container made of a material having excellent flexibility and steam permeability are broadly classified into a type in which the filter element is welded to a sheet-like flexible frame, which is then welded to a housing material (see European Patent Specification EP 0526678 and Japanese Patent Laid-Open No. 11-216179), and a type in which a flexible container is directly welded to the filter element (see Japanese Patent Laid-Open No. 7-267871 and International Publication No. WO 95/17236). The former type may be hereinafter referred to as “frame welding type” and the latter may be referred to as “container welding type”.
Normally, when processing blood with these types of leukocyte removal filters, a bag containing a blood preparation to be processed that is connected to a blood inlet side of the filter via a tube is placed at a height that is approximately 20 to 100 cm higher than the filter to allow the blood preparation to pass through the filter by the action of gravity. After filtration, the blood preparation is stored in a recovery bag that is connected to a blood outlet side of the filter via a tube. During filtration, a pressure loss occurs due to the resistance of the filter element, whereby the pressure in a space on the inlet side of the filter becomes a positive pressure. In the case of the filter that includes a flexible container, there is a tendency for the flexibility of the container itself to cause the container to swell like a balloon due to the positive pressure, thereby pressing the filter element against the container on the outlet side.
Furthermore, normally, a bag for storing blood that has been processed with the blood filter is placed at a position that is 50 to 100 cm lower than the filter, and blood moves through a channel on the downstream side due to the action of gravity. Hence, there is a tendency for the outlet side of the filter to become a negative pressure due to this action, and the flexible container is liable to adhere to the filter element.
That is, it has been pointed out previously that in the case of a filter that uses a flexible container, there is a problem that there is a strong tendency for the filter element to adhere to the outlet-side container due to a dual force, and as a result the flow of blood is obstructed and an adequate flow rate can not be obtained.
Various measures have been proposed to solve this problem. Representative examples of such measures include a method that inserts a soft polyvinyl chloride tube referred to as a “connecting rod” between the filter element and the outlet-side container to prevent adherence (see European Patent Specification EP 0526678), a method that prevents adherence by providing concavities and convexities with vertical intervals of 0.2 mm to 2 mm on the internal surface of a soft container (Japanese Patent Laid-Open No. 11-216179), and a method that inserts a screen made of knit fiber (International Publication No. WO 95/17236).
However, in a case in which a separate member such as a connecting rod or a screen is inserted, because it is required to perform welding precisely when welding the separate member to the container, there are the problems that a welding defect may occur, the manufacturing process is complicated, and the manufacturing cost is increased by the use of additional materials.
Furthermore, in the case of providing concavities and convexities on the internal surface of a container, there is the problem that the concavities and convexities on the internal surface of the container may induce a welding defect or may decrease the pressure resistance when the container material and the filter element are welded together.
Further, in a filter in which at least one of an inlet and an outlet is straddled and sealed by a second seal part, as disclosed in European Patent Specification EP 0526678, Japanese Patent Laid-Open No. 11-216179, and international Publication No. WO 04/050147, it is necessary to use a complicated tool or process used for sealing.
As described above, when the conventional technology is investigated from the point of view of a disadvantage caused by negative pressure that arises on the filter outlet side, in other words, from the point of view of how to secure a space that can serve as a passage for blood to pass through between the container and the filter element that are attempting to adhere to each other, it is found that the conventional technology is not necessarily satisfactory.